Our major goal is to enhance understanding regarding the role of pulmonary, aortic, carotid and intracranial chemoreceptors in the hyperpnea elicited by CO2 inhalation. We also wish to further insight regarding regulation during CO2 exposure of core temperature, VO2, tissue stores of CO2 and acid-base status of cerebrospinal fluid (CSF) and cerebral interstitial fluid (ISF). In years 1 and 2, unanesthetized spontaneously breathing ponies will be studied while breathing ambient air, during 15 minutes when the (CO2) of an environmental chamber is increased to 1-6%, during acute hypoxia, and during i.v. injections of NaCN and coxapram HCl. This series of studies will be completed over 4-5 days, once before, again 1 week after, and every 2nd to 4th month after surgical excision of the arterial chemoreceptors. Arterial blood will be sampled from indwelling catheters, and pulmonary ventilation (VE) and respiratory timing will be measured using the transthoracic impedance technique. Two areas of interest are: 1) the role of the arterial chemoreceptors in the apparent isocapnic hyperpnea breathing 1-4% CO2, and 2) the effect of chemoreceptor excision on VE and respiratory timing. In year 2, we will also study a second group of ponies in which, through chronic traceostomy and acute bronchospirometry, we can investigate the effect on VE and respiratory timing of altering (CO2) in selective portions of pulmonary airways. In year 3, we will study normal ponies before and during 2 weeks of exposure to 3% CO2 in an environmental chamber. Mock CSF of varying (HCO3 minus) and (Cl minus) will be perfused through the cerebral ventricles and the cisterna magna to provide information on: 1) ionic composition of cerebral ISF, and 2) the role of the intracranial chemoreceptor in regulation of VE during CO2 inhalation. We will also study the potential role in the CO2 breathing hyperpnea of plasma and CSF concentrations of H plus, NH3 and norepinephrine, and of pulmonary and systemic hemodynamics. Finally, we will determine the interrelation during CO2 exposure between core temperature, VO2, tissue CO2 stores, and urinary and plasma concentrations of norepinephrine, Ca ions, HPO4 minus and H plus.